For many ions and molecules, the major entry pathway into central nervous system is by way of the choroid plexus, i.e., the blood-CSF barrier. Choroid plexus function in immature mammals is substantially different than in adults; for example in the ability of the tissue to secrete cerebrospinal fluid and to respond to perturbations in blood chemistry. The current and proposed ontogenetic projects are concerned with analyzing the protective role of the choroid plexus (kidney-like function) in stabilizing the composition and volume of the extracellular fluid in brain. Developmental aspects of neurohumoral and pharmacological modulation of ion transport (i.e., C1-HCO3; Na-H; and Na-Ca exchangers) are to be investigated in the developing choroid plexus. Both in vitro and in vivo systems will be employed; in the latter model, the functional interrelationships among choroid plexus, cerebrospinal fluid and various brain regions will be analyzed. The effects of neurotransmitters, hormones and drugs on ion translocation across apical and basolateral membranes of CP will be investigated in 1-, 3- and 6-wk-old Sprague-Dawley rats. The procured transport and permeability data will characterize capacity, localization and regulation of cation and anion exchangers in the blood-CSF barrier. Therapeutic amelioration of problems resulting from cerebral edema, hydrocephalus, alteration of brain and CSF pH, etc. will be feasible when a better understanding is gained about neurohumoral regulation of distribution of chloride, bicarbonate, sodium, potassium, hydrogen, and calcium ions between blood, choroid plexuses, cerebrospinal fluid, and various regions of brain. The physiological/pharmacological data to be obtained will enhance appreciation of the coupling of receptor activity to ion translocation processes; analysis of this regulatory problem at the biochemical and structural level is the long-term goal of future projects.